PUBLICATION
Identification of a functional susceptibility variant for adolescent idiopathic scoliosis that upregulates EGR1-mediated UNCX expression
- Authors
- Yonezawa, Y., Guo, L., Kakinuma, H., Otomo, N., Yoshino, S., Takeda, K., Nakajima, M., Shiraki, T., Ogura, Y., Takahashi, Y., Koike, Y., Minami, S., Uno, K., Kawakami, N., Ito, M., Yonezawa, I., Watanabe, K., Kaito, T., Yanagida, H., Taneichi, H., Harimaya, K., Taniguchi, Y., Shigematsu, H., Iida, T., Demura, S., Sugawara, R., Fujita, N., Yagi, M., Okada, E., Hosogane, N., Kono, K., Chiba, K., Kotani, T., Sakuma, T., Akazawa, T., Suzuki, T., Nishida, K., Kakutani, K., Tsuji, T., Sudo, H., Iwata, A., Sato, T., Inami, S., Nakamura, M., Matsumoto, M., Terao, C., Watanabe, K., Okamoto, H., Ikegawa, S.
- ID
- ZDB-PUB-221108-14
- Date
- 2022
- Source
- Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 38(1): 144-153 (Journal)
- Registered Authors
- Shiraki, Toshiyuki
- Keywords
- none
- MeSH Terms
-
- Animals
- Genetic Predisposition to Disease
- Genome-Wide Association Study*
- Polymorphism, Single Nucleotide/genetics
- Scoliosis*/genetics
- Transcription Factors/genetics
- Zebrafish/genetics
- PubMed
- 36342191 Full text @ J. Bone Miner. Res.
Citation
Yonezawa, Y., Guo, L., Kakinuma, H., Otomo, N., Yoshino, S., Takeda, K., Nakajima, M., Shiraki, T., Ogura, Y., Takahashi, Y., Koike, Y., Minami, S., Uno, K., Kawakami, N., Ito, M., Yonezawa, I., Watanabe, K., Kaito, T., Yanagida, H., Taneichi, H., Harimaya, K., Taniguchi, Y., Shigematsu, H., Iida, T., Demura, S., Sugawara, R., Fujita, N., Yagi, M., Okada, E., Hosogane, N., Kono, K., Chiba, K., Kotani, T., Sakuma, T., Akazawa, T., Suzuki, T., Nishida, K., Kakutani, K., Tsuji, T., Sudo, H., Iwata, A., Sato, T., Inami, S., Nakamura, M., Matsumoto, M., Terao, C., Watanabe, K., Okamoto, H., Ikegawa, S. (2022) Identification of a functional susceptibility variant for adolescent idiopathic scoliosis that upregulates EGR1-mediated UNCX expression. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 38(1):144-153.
Abstract
Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome-wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX mRNA injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping